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A patatin-like phospholipase mediates Rickettsia parkeri escape from host membranes

Author

Listed:
  • Gina M. Borgo

    (University of California, Berkeley
    University of California, Berkeley)

  • Thomas P. Burke

    (University of California, Berkeley
    University of California, Irvine)

  • Cuong J. Tran

    (University of California, Berkeley
    University of California, Berkeley)

  • Nicholas T. N. Lo

    (University of California, Berkeley)

  • Patrik Engström

    (University of California, Berkeley
    Primordial Genetics)

  • Matthew D. Welch

    (University of California, Berkeley)

Abstract

Rickettsia species of the spotted fever group are arthropod-borne obligate intracellular bacteria that can cause mild to severe human disease. These bacteria invade host cells, replicate in the cell cytosol, and spread from cell to cell. To access the host cytosol and avoid immune detection, they escape membrane-bound vacuoles by expressing factors that disrupt host membranes. Here, we show that a patatin-like phospholipase A2 enzyme (Pat1) facilitates Rickettsia parkeri infection by promoting escape from host membranes and cell-cell spread. Pat1 is important for infection in a mouse model and, at the cellular level, is crucial for efficiently escaping from single and double membrane-bound vacuoles into the host cytosol, and for avoiding host galectins that mark damaged membranes. Pat1 is also important for avoiding host polyubiquitin, preventing recruitment of autophagy receptor p62, and promoting actin-based motility and cell-cell spread.

Suggested Citation

  • Gina M. Borgo & Thomas P. Burke & Cuong J. Tran & Nicholas T. N. Lo & Patrik Engström & Matthew D. Welch, 2022. "A patatin-like phospholipase mediates Rickettsia parkeri escape from host membranes," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31351-y
    DOI: 10.1038/s41467-022-31351-y
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    References listed on IDEAS

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    1. Jacqueline Staring & Eleonore von Castelmur & Vincent A. Blomen & Lisa G. van den Hengel & Markus Brockmann & Jim Baggen & Hendrik Jan Thibaut & Joppe Nieuwenhuis & Hans Janssen & Frank J. M. van Kupp, 2017. "PLA2G16 represents a switch between entry and clearance of Picornaviridae," Nature, Nature, vol. 541(7637), pages 412-416, January.
    2. Mark A. Czuczman & Ramzi Fattouh & Jorik M. van Rijn & Veronica Canadien & Suzanne Osborne & Aleixo M. Muise & Vijay K. Kuchroo & Darren E. Higgins & John H. Brumell, 2014. "Listeria monocytogenes exploits efferocytosis to promote cell-to-cell spread," Nature, Nature, vol. 509(7499), pages 230-234, May.
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    Cited by:

    1. Allen G. Sanderlin & Hannah Kurka Margolis & Abigail F. Meyer & Rebecca L. Lamason, 2024. "Cell-selective proteomics reveal novel effectors secreted by an obligate intracellular bacterial pathogen," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Michele Castelli & Tiago Nardi & Leandro Gammuto & Greta Bellinzona & Elena Sabaneyeva & Alexey Potekhin & Valentina Serra & Giulio Petroni & Davide Sassera, 2024. "Host association and intracellularity evolved multiple times independently in the Rickettsiales," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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